Doppler Ultrasonography of Fetal Anemia in Alloimmunized Pregnancies

Question

What can I do for a pregnant woman who is at 24 weeks' gestation with a twin pregnancy and who has an anti-Rhesus (Rh) titer of 1/32 (since 18 weeks)? Fetal echographic changes were not detected. Would anti-Rh immune globulin (RhoGAM) help at this point? What is the role of Doppler ultrasonography in determining fetal anemic status?

Since the introduction of ultrafiltered Rho(D) immune globulin (RhoGAM) in the 1960s, Rhesus (Rh) alloimmunization and the associated fetal and neonatal complications have become much less common. However, as the result of either inadvertent omission of Rho(D) immune globulin administration at delivery or termination or possibly unrecognized spontaneous abortion or another episode of unrecognized fetal-maternal hemorrhage, Rh-sensitization still occurs in approximately 1 to 6 per 1000 live births.[1]

The first step in evaluation of a newly diagnosed Rh-sensitized woman is checking maternal titer. In most centers, the critical value for anti-Rh titers is between 1:8 and 1:32. In general, a woman's first sensitized pregnancy incurs minimal fetal/neonatal disease, but a worsening degree of anemia occurs with each subsequent gestation. In the setting of a previously affected fetus, infant titers are not predictive of degree of anemia.[1]

Once sensitization is detected in a pregnant woman without a history of an affected pregnancy, maternal titers should be repeated monthly until 24 weeks and then subsequently every 2 weeks. Additionally, once a pregnant woman becomes sensitized, there is no role for Rh immunoglobulin administration.

For the sensitized pregnant woman, paternal blood can be drawn to determine Rh status and zygosity if paternity is certain. If the father is Rh-positive and heterozygous or paternity is uncertain, amniocentesis can be offered to determine fetal blood type once a critical titer is reached. If the father is Rh-negative, or the fetus is determined to be Rh-negative, further monitoring is not indicated.[1]

If the fetus is determined to be Rh-positive, fetal surveillance for evidence of anemia is crucial. Previously, standard surveillance was done with serial amniocentesis using spectral analysis of amniotic fluid at 450 nm (deltaOD450) to measure the level of bilirubin as an indicator of the degree of fetal hemolysis. Serial amniocentesis every 10 to 14 days was performed, and if a deltaOD450 in the 80th percentile of zone 2 of the Liley curve or a value in the transfusion zone of the Queenan curve was noted, fetal blood sampling with transfusion was undertaken. If no increase in deltaOD450 is detected on amniocentesis at 37 weeks, fetal lung maturity studies are indicated and induction can follow instead of further amniocentesis.[1]

Ultrasound has been used as a tool in the evaluation of fetuses in Rh-isoimmunized pregnancies. Fetal hydrops, usually preceded by ascites, is easily detected by ultrasound but is indicative of severe hemolytic disease, with fetal hemoglobin often one third of normal or less. In recent years, there has been a movement toward noninvasive surveillance using Doppler ultrasonography to detect early evidence of fetal anemia in alloimmunized pregnancies.[1] In the mid-1990s, it was reported that in fetuses with anemia, an increased peak velocity of systolic blood flow in the middle cerebral artery (MCA) could be detected with Doppler ultrasound studies.[2] Since then, MCA Doppler studies have proved to be accurate in the determination of the development of fetal anemia in Rh-isoimmunized pregnancies[3,4]; they are also used to follow fetal response to intrauterine transfusion and to assist in timing subsequent transfusions.[5,6]

To obtain MCA peak systolic velocity (MCA PSV) measurements, the fetal MCA closest to the maternal skin should be measured using a minimal angle of insonation with the Doppler gate placed over the vessel as it bifurcates from the carotid siphon. Color can be used to determine correct location. Serial MCA Doppler studies can be used to generate a curve that plots MCA peak systolic velocity as a function of gestational age. At the time when moderate-to-severe anemia is seen, fetal blood sampling with transfusion can be undertaken. After 35 weeks' gestation, accuracy in determining MCA PSV appears to decrease; therefore, at this gestational age amniocentesis for deltaOD450 may be indicated.[1]

Given that MCA Doppler ultrasound reliably depicts fetal anemia and poses less risk to the patient and fetus secondary to the noninvasive nature of ultrasound, the question arises as to how Rh-isoimmunized patients now should be managed. In a recent review,[7] Dr. Mari addresses this question by stating that if there is an imaging center with sonographers and sonologists who are well trained to assess MCA PSV, then treatment of patients at risk for fetal anemia being followed at that center should be based on MCA PSV. If there are no centers nearby performing MCA PSV, untrained personnel should not perform this test. Patients should be informed of the available options for the management of Rh-isoimmunized pregnancies, and the option of serial amniocentesis should be presented.

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